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Identification and Validation of the Immune Regulator CXCR4 as a Novel Promising Target for Gastric Cancer

作者:Shuai Xue, Ming Ma, Songhua Bei, Fan Li, Chenqu Wu, Huanqing Li, Yanling Hu, Xiaohong Zhang, Yanqing Qian, Zhe Qin, Jun Jiang, Li Feng · 发表于:Frontiers in Immunology · 年份:2021 · DOI:10.3389/fimmu.2021.702615 · 被引用次数:23 · 研究领域:Cancer Mechanisms and Therapy、Gastric Cancer Management and Outcomes、Cancer Immunotherapy and Biomarkers

Immune checkpoint blockade has attracted a lot of attention in the treatment of human malignant tumors. We are trying to establish a prognostic model of gastric cancer (GC) based on the expression profile of immunoregulatory factor-related genes. Based on the TCGA database, we identified 234 differentially expressed immunoregulatory factors. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) conducted enrichment analysis to clarify the biological functions of differential expression of immunoregulatory factors. STRING database predicted the interaction network between 234 differently expressed immune regulatory factors. The expression of 11 immunoregulatory factors was significantly related to the overall survival of gastric cancer patients. Univariate Cox regression analysis, Kaplan–Meier analysis and multivariate Cox regression analysis found that immunomodulatory factors were involved in the progression of gastric cancer and promising biomarkers for predicting prognosis. Among them, CXCR4 was related to the low survival of GC patients and a key immunomodulatory factor in GC. Based on TCGA data, the high expression of CXCR4 in GC was positively correlated with the advanced stage and grade of gastric cancer and related to poor prognosis. Univariate analysis and multivariate analysis indicated that CXCR4 was an independent prognostic indicator for TCGA gastric cancer patients. In vitro functional studies had shown that CXCR4 promoted the proliferation, migr...